A Phase II, Single-blind, Randomized, Placebo-controlled Trial to Study the Efficacy and Safety of Anti-von Willebrand Factor Nanobody Administered as Adjunctive Treatment to Patients With Acquired Thrombotic Thrombocytopenic Purpura

Ablynx, a Sanofi company1 site in 1 country75 target enrollmentJanuary 2011

ConditionsAcquired Thrombotic Thrombocytopenic Purpura

Overview

Phase: Phase 2
Intervention: Not specified
Conditions: Acquired Thrombotic Thrombocytopenic Purpura
Sponsor: Ablynx, a Sanofi company
Enrollment: 75
Locations: 1
Primary Endpoint: Time-to-response of Treatment Defined by a Confirmed Recovery of Platelets ≥ 150,000/µL
Status: Completed
Last Updated: 3 years ago

Overview Investigators Eligibility Criteria Outcomes Sites Similar Trials

Overview

Brief Summary

This study was a Phase II, single-blind, randomized, placebo-controlled trial to determine whether anti-vWF Nanobody is safe and effective as adjunctive treatment in patients with aTTP.

Patients received either placebo or anti-vWF Nanobody as adjunctive therapy to plasma exchange (PE).

Registry

clinicaltrials.gov

Start Date

January 2011

End Date

March 2014

Last Updated

3 years ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Ablynx, a Sanofi company

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•18 years of age or older (adults) or aged 12 to \< 18 years (adolescents)
•Male or female subject, willing to accept an acceptable contraceptive regimen
•Subject with a clinical diagnosis of TTP
•Requiring PE (one single PE session prior to randomization into the study was allowed)
•Subject accessible to follow-up
•Subject able to provide signed and dated informed consent and assent (if applicable, for adolescents)

Exclusion Criteria

•Platelet count ≥ 100,000/µL
•Severe active infection indicated by sepsis (requirement for pressors with or without positive blood cultures)
•Clinical evidence of enteric infection with Escherichia coli 0157 or related organism
•Anti-phospholipid syndrome
•Diagnosis of disseminated intravascular coagulation (DIC)
•Pregnancy or breast-feeding
•Hematopoietic stem cell or bone marrow transplantation-associated thrombotic microangiopathy
•Known with congenital TTP
•Active bleeding or high risk of bleeding
•Uncontrolled arterial hypertension

Outcomes

Primary Outcomes

Time-to-response of Treatment Defined by a Confirmed Recovery of Platelets ≥ 150,000/µL

Time Frame: From the day of first study drug administration up to 30 days after first study drug administration

Time-to-response, defined by the achievement of platelet count response, confirmed at 48 hours after the initial reporting of this response. Platelet response was defined as recovery of platelets ≥ 150,000/µL. This response had to be confirmed at 48 hours after the initial reporting of platelet recovery ≥ 150,000/µL by a de novo measure of platelets ≥ 150,000/µL and lactate dehydrogenase (LDH) ≤ 2x upper limit of normal (ULN) (i.e., 'confirmed platelet response').

Secondary Outcomes

Number of Daily PE Sessions During the Initial Daily PE Period(During the initial daily PE period, with a median (min, max) duration of exposure to study drug of 6 (2, 36) days)
Number of Days With at Least One PE Administration During the Total Course of the Study(During the total course of the study (from Screening till the 12-month follow-up [FU] visit))
Number of TEAEs and Their Relationship to Study Drug(From the start of the study up to 1 month follow-up)
Pharmacodynamics (PD): Ristocetin Cofactor (RICO) Activity Over Time(From the start of the study up to 1 month follow-up (i.e., at Baseline, Days 1 and 2 of daily PE, last day of daily PE, Day 1 after daily PE, Weeks 1, 2, 3, and 4 after daily PE, Days 3 and 7 of FU and at the 1-month FU visit).)
The Maximum Number of Consecutive Days Per Subject Where There Was no Interruption of PE During the Initial Daily PE Period(During the initial daily PE period, with a median (min, max) duration of exposure to study drug of 6 (2, 36) days)
Number of Treatment-emergent Adverse Events (TEAEs) by Severity(From the start of the study up to 1 month follow-up)
Number and Percentage of Subjects With TEAEs by Severity(From the start of the study up to 1 month follow-up)
Number of Participants Who Developed Treatment-emergent Anti-Drug Antibodies (ADA)(From the start of the study until last follow-up visit)
Pharmacodynamics: Von Willebrand Factor Antigen (vWF:Ag) Over Time(From the start of the study drug up to 1 month follow-up (i.e., at Baseline, Days 1 and 2 of daily PE, last day of daily PE, Day 1 after daily PE, Weeks 1, 2, 3, and 4 after daily PE, Days 3 and 7 of FU and at the 1-month FU visit).)
Resolution of Non-focal Neurological Symptoms(From Baseline till the 12-month FU visit)
Number of Participants With Resolution of TTP-related Signs or Symptoms(End of daily PE treatment period (median [min, max] duration of exposure to study drug of 6 [2, 36] days), end of study treatment period (median [min, max] duration of exposure to study drug of 36.5 [2, 90] days) and at 1 month follow-up)
Mortality(From the start of the study up to 1 month follow-up)
Number of PE Related Adverse Events(From the start of the study up to 1 month follow-up)
Plasma Concentrations of Caplacizumab(From the start of the study up to 1 month follow-up (i.e., at Baseline, Days 1 and 2 of daily PE, last day of daily PE, Day 1 after daily PE, Weeks 1, 2, 3, and 4 after daily PE, Days 3 and 7 of FU and at the 1-month FU visit).)
PD: Coagulation Factor VIII Clotting Activity (FVIII:C) Over Time(From the start of the study up to 1 month follow-up (i.e., at Baseline, Days 1 and 2 of daily PE, last day of daily PE, Day 1 after daily PE, Weeks 1, 2, 3, and 4 after daily PE, Days 3 and 7 of FU and at the 1-month FU visit).)
Number and Percentage of Subjects With Complete Remission Following Initial Daily Plasma Exchange (PE)(From the day of first study drug administration up to 30 days after first study drug administration)
Number and Percentage of Subjects With Relapse of TTP(Later than 30 days after the last daily PE)
Total Volume of Plasma Administered During the Initial Daily PE Period(During the initial daily PE period, with a median (min, max) duration of exposure to study drug of 6 (2, 36) days)
Number and Percentage of Subjects With Exacerbations of TTP(Within 30 days of last day of initial daily PE)
Number and Percentage of Subjects With PE Related AEs(From the start of the study up to 1 month follow-up)